HIF signaling mediates cellular responses to low oxygen by stabilizing HIF-α transcription factors and activating HRE-linked target genes. The review presents it as a central disease-relevant signaling axis in zebrafish models.
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hypoxia-inducible factor signaling
Candidate: concept label3 source documents13 linked claims
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HIF-mediated hypoxia response, HIF signaling
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This review explores the diverse functions of hypoxia-inducible factor (HIF) signaling in cancer development and progression.
Disrupted hypoxia sensing-exemplified by deficient hypoxia-inducible factor (HIF) signaling-leads to placental maldevelopment, while sustained HIF activation drives preeclampsia-like pathology.
In this Review, we discuss recent advances in our understanding of hypoxia and HIFs in disease that have emerged from studies of zebrafish disease models.
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In cancer, HIF signaling promotes angiogenesis through upregulation of VEGF expression, enhances the Warburg effect, facilitates invasion and metastasis through EMT and matrix remodeling, and mediates therapeutic resistance partly via drug efflux pumps and DNA damage repair.
Oxygen-dependent hydroxylation of proline and asparagine residues in HIF-α subunits is a key regulatory mechanism for HIF stability and transcriptional function.
HIF-1α and HIF-2α regulate genes linked to invasion, metabolic reprogramming, angiogenesis, and therapy resistance and mediate a significant portion of the hypoxic response.
Hypoxia drives cancer progression through immune modulation, angiogenesis promotion, metabolic reprogramming, and uncontrolled cell proliferation.
HIF signaling is regulated by ERK/MAPK, PI3K/Akt/mTOR, and JAK/STAT pathways.
Deficient HIF signaling leads to placental maldevelopment.
Quoted textsource-backed
Disrupted hypoxia sensing-exemplified by deficient hypoxia-inducible factor (HIF) signaling-leads to placental maldevelopment
Sustained HIF activation drives preeclampsia-like pathology.
Quoted textsource-backed
while sustained HIF activation drives preeclampsia-like pathology
The HIF-mediated hypoxia response is increasingly recognized as an important determinant of disease outcome in cancer, inflammatory disease, and bacterial infections.
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the HIF-mediated hypoxia response is being increasingly recognised as an important process in determining the outcome of diseases such as cancer, inflammatory disease and bacterial infections.
Cellular hypoxia is sensed by oxygen-sensitive hydroxylase enzymes that regulate the protein stability of HIF-α transcription factors.
Quoted textsource-backed
Cellular hypoxia is sensed by oxygen-sensitive hydroxylase enzymes, which regulate the protein stability of hypoxia-inducible factor α (HIF-α) transcription factors.
Stabilized HIF-α binds with cofactors to HREs in target-gene promoters to coordinate a broad transcriptional response to hypoxia.
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When stabilised, HIF-α binds with its cofactors to HIF-responsive elements (HREs) in the promoters of target genes to coordinate a wide-ranging transcriptional programme in response to the hypoxic environment.
Animal models have revealed HIF roles in disease and multicellular control mechanisms that may be missed in simpler in vitro systems.
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Animal models have shed light on the roles of HIF in disease and have uncovered intricate control mechanisms that involve multiple cell types, observations that might have been missed in simpler in vitro systems.
Findings from zebrafish disease models identify HIF as an integral player in disease processes.
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Findings from such models identify HIF as an integral player in the disease processes.
HIF pathway components and their targets are highlighted as potential therapeutic targets for diseases ranging from cancers to infectious disease.
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They also highlight HIF pathway components and their targets as potential therapeutic targets against conditions that range from cancers to infectious disease.